Expression of integrins in human proliferative diabetic retinopathy membranes

Ning, Allison; Cui, Jing; Maberley, David; Ma, Patrick; Matsubara, Joanne A.

doi:10.3129/i08-145

Cited by 18 publications

(14 citation statements)

References 22 publications

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“…Integrins, such as a v b 3 , a v b 5 , a 5 b 1 and a 2 b 1 , promote angiogenesis by mediating cell migration, proliferation and survival of angiogenic endothelial cells [133]. Recently, we demonstrated that only a v b 3 integrin was expressed in PDR epiretinal membranes and was specifically localized in vascular endothelial cells and stromal cells [17]; similar findings were noted by Ning et al [134]. Integrin a v b 3 has been especially identified as a marker of angiogenesis because it is expressed on angiogenic blood vessels in human wound granulation tissue but not in normal skin.…”

supporting

confidence: 68%

“…Its expression increased during angiogenesis on the chick chorioallantoic membrane. In the latter assay, a monoclonal antibody to a v b 3 blocked angiogenesis induced by basic FGF, TNF-a and human melanoma fragments but had no effect on pre-existing vessels [134]. Ligation of integrin a v b 3 is required for the survival and maturation of newly forming blood vessels.…”

mentioning

confidence: 99%

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Pathophysiology and management of diabetic retinopathy

El‐Asrar¹,

Al-Mezaine

Ola

2009

Expert Review of Ophthalmology

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Diabetic retinopathy remains a major cause of worldwide preventable blindness. In this review, we evaluate the recent advances in understanding the molecular mechanisms of diabetic retinopathy, highlight the current management of diabetic retinopathy and new therapeutic approaches, and discuss the range of potential future therapeutic strategies in order to combat the disease. The microvasculature of the retina responds to hyperglycemia through a number of biochemical changes, including the activation of PKC, increased advanced glycation endproducts formation, polyol pathway and oxidative stress, and activation of the renin-angiotensin system. There is an accumulating body of evidence that inflammation and neurodegeneration play a prominent role in the pathogenesis of diabetic retinopathy. Strict metabolic control, tight blood pressure control, laser photocoagulation and vitrectomy remain the standard care for diabetic retinopathy. Emerging therapies include intravitreal triamcinolone or anti-VEGF agents, ruboxistaurin, renin-angiotensin system blockers, fenofibrate, islet cell transplantation, PPAR-g agonists and intravitreal hyaluronidase. However, more randomized, controlled clinical trials are required to clarify their role alone or in combination. Learning objectivesUpon completion of this activity, participants should be able to:• Identify factors that contribute to the development of diabetic retinopathy Medscape: Continuing Medical Education OnlineThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of MedscapeCME and Expert Reviews Ltd. MedscapeCME is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. MedscapeCME designates this educational activity for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test and/or complete the evaluation at http://cme.medscape.com/CME/expertreviews; (4) view/print certificate. For reprint orders, please contact reprints@expert-reviews.comExpert Rev. Ophthalmol. 4(6), (2009) 628Review Abu El-Asrar, Al-Mezaine & Ola CME Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and remains one of the leading causes of blindness worldwide among adults aged 20-74 years. The two most important visual complications of DR are diabetic macular edema (DME) and proliferative DR (PDR). The prevalence of DR increases with the duration of diabetes, and nearly all people with Type 1 diabetes, and more than 60% of those with Type 2, have some retinopathy after 20 years. In the Wisconsin Epide...

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supporting

confidence: 68%

mentioning

confidence: 99%

Pathophysiology and management of diabetic retinopathy

El‐Asrar¹,

Al-Mezaine

Ola

2009

Expert Review of Ophthalmology

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“…Only αvβ3 and β3 integrin proteins were found to be moderately induced and specifically co-localized with endothelial cell markers in two of the four patients with PDR tested. While further validation is required, these data suggest a specific impact of PDR on a subset of integrins, which could reflect their role in pathological angiogenesis [21] . Perturbations of the retinal vasculature associated with diabetes have long been known from animal models, but studies using tissues from human donors continue to be key to our understanding of the molecular mechanisms underlying the vascular changes associated with the different stages of DR.…”

Section: Neo-angiogenesismentioning

confidence: 92%

“…A study conducted by Friedlander et al [20] in animal models of angiogenesis suggested that since αvβ3 and αvβ5 integrins were involved in angiogenesis, these specific integrins could be critical in PDR. Ning et al [21] utilized this data to expand upon and determine the co-localization of five different integrins with the retinal vascular endothelium of four patients with PDR. Contrary to what was found in the animal models, no staining was observed for αvβ5 integrins, possibly attributed to inter-species variability.…”

Section: Neo-angiogenesismentioning

confidence: 98%

Current knowledge on diabetic retinopathy from human donor tissues

Eisma

Dulle

Fort

2015

WJD

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According to the American Diabetes Association, diabetes was the seventh leading cause of death, and diabetic retinopathy the leading cause of blindness in working age adults in the United States in 2010. Diabetes is characterized by hyperglycemia associated with either hypoinsulinemia or insulin resistance, and over time, this chronic metabolic condition may lead to various complications including kidney failure, heart attacks, and retinal degeneration. In order to better understand the molecular basis of this disease and its complications, animal models have been the primary approach used to investigate the effects of diabetes on various tissues or cell types of the body, including the retina. However, inherent to these animal models are critical limitations that make the insight gained from these models challenging to apply to the human pathology. These difficulties in translating the knowledge obtained from animal studies have led a growing number of research groups to explore the diabetes complications, especially diabetic retinopathy, on tissues from human donors. This review summarizes the data collected from diabetic patients at various stages of diabetic retinopathy and classifies the data based upon their relevance to the main aspects of diabetic retinopathy: retinal vasculature dysfunction, inflammation, and neurodegeneration. This review discusses the importance of those studies to discriminate and establish the relevance of the findings obtained from animal models but also the limitations of such approaches.

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“…A number of studies have shown that integrins are implicated in pathologic angiogenesis in the retina. Integrin α v β3 has been found localized in retinal neovascular tissue removed from patients with proliferative diabetic retinopathy 78. In the mouse model of OIR, inhibition of α v β3 and α v β5 using a nonpeptidic antagonist reduced neovascular area, and VEGF and VEGFR2 expression in the retina 79.…”

Section: Signaling Pathways Involved In Vegf Expression and Vegf-medimentioning

confidence: 99%

Anti-VEGF therapy in the management of retinopathy of prematurity: what we learn from representative animal models of oxygen-induced retinopathy

Wang

2016

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Retinopathy of prematurity (ROP) remains a leading cause of childhood blindness, affecting infants born prematurely. ROP is characterized by the onset of delayed physiological retinal vascular development (PRVD) and followed by pathologic neovascularization into the vitreous instead of the retina, called intravitreal neovascularization (IVNV). Therefore, the therapeutic strategy for treating ROP is to promote PRVD and inhibit or prevent IVNV. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of ROP. There is a growing body of studies testing the use of anti-VEGF agents as a treatment for ROP. Intravitreal anti-VEGF treatment for ROP has potential advantages compared with laser photocoagulation, the gold standard for the treatment of severe ROP; however, intravitreal anti-VEGF treatment has been associated with reactivation of ROP and suppression of systemic VEGF that may affect body growth and organ development in preterm infants. Therefore, it is important to understand the role of VEGF in PRVD and IVNV. This review includes the current knowledge of anti-VEGF treatment for ROP from animal models of oxygen-induced retinopathy (OIR), highlighting the importance of VEGF inhibition by targeting retinal Müller cells, which inhibits IVNV and permits PRVD. The signaling events involved in mediating VEGF expression and promoting VEGF-mediated angiogenesis, including hypoxia-dependent signaling, erythropoietin/erythropoietin receptor-, oxidative stress-, beta-adrenergic receptor-, integrin-, Notch/Delta-like ligand 4- and exon guidance molecules-mediated signaling pathways, are also discussed.

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Expression of integrins in human proliferative diabetic retinopathy membranes

Cited by 18 publications

References 22 publications

Pathophysiology and management of diabetic retinopathy

Pathophysiology and management of diabetic retinopathy

Current knowledge on diabetic retinopathy from human donor tissues

Anti-VEGF therapy in the management of retinopathy of prematurity: what we learn from representative animal models of oxygen-induced retinopathy

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